Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1.   Pharmacodynamic properties

Pharmacotherapeutic group: Antibacterial for systemic use, macrolide

ATC-Code: J01FA09
Mode of Action:

Clarithromycin is an antibiotic belonging to the macrolide antibiotic group. It exerts its anti- bacterial action by selectively binding to the 50s ribosomal sub-unit of susceptible bacteria preventing translocation of activated amino acids. It inhibits the intracellular protein synthesis of susceptible bacteria.

The 14-hydroxy metabolite of clarithromycin, a product of parent drug metabolism also has anti-microbial activity. The metabolite is less active than the parent compound for most organisms, including mycobacterium spp. An exception is Haemophilus influenza where the 14-hydroxy metabolite is two-fold more active than the parent compound.


Clarithromycin is also bactericidal against several bacterial strains.
Clarithromycin is usually active against the following organisms in vitro:- Gram-positive Bacteria: Staphylococcus aureus (methicillin susceptible); Streptococcus pyogenes (Group A beta-haemolytic streptococci); alpha-haemolytic streptococci (viridans group); Streptococcus (Diplococcus) pneumoniae; Streptococcus agalactiae; Listeria monocytogenes.

Gram-negative Bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae; Legionella pneumophila, Bordetella pertussis, Helicobacter pylori; Campylobacter jejuni.

Mycoplasma: Mycoplasma pneumoniae; Ureaplasma urealyticum.

Other Organisms: Chlamydia trachomatis; Mycobacterium avium; Mycobacterium leprae; Chlamydia pneumoniae.

Anaerobes: Macrolide-susceptible Bacteroides fragilis; Clostridium perfringens; Peptococcus species; Peptostreptococcus species; Propionibacterium acnes.

Clarithromycin also has bactericidal activity against several bacterial strains. These organisms include H. influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Moraxella (Brahamella) catarrhalis, Neisseria gonorrhoeae, Helicobacter pylori and Campylobacter species.

Breakpoints

The following breakpoints have been established by the European Committee for Antimicrobial Susceptibility Testing (EUCAST).

Breakpoints (MIC, mg/L)
Microorganism                    Susceptible (≤)              Resistant (>) Staphylococcus spp.              1 mg/L                       2 mg/L
Streptococcus A, B, C and G      0.25 mg/L                    0.5 mg/L Streptococcus pneumonia          0.25 mg/L                    0.5 mg/L Viridans group streptococcus     IE                           IE
Haemophilus spp.                 1 mg/L                       32 mg/L Moraxella catarrhalis            0.25 mg/L                    0.5 mg/L 1 Helicobacter pylori             0.25 mg/L1                 0.5 mg/L
1
The breakpoints are based on epidemiological cut-off values (ECOFFs), which distinguish wild-type isolates from those with reduces susceptibility.

“IE" indicates that there is insufficient evidence that the species in question is a good target for therapy with the drug.

Pharmacokinetic Properties

5.2.      Pharmacokinetic properties
Clarithromycin is rapidly and well absorbed from the gastro-intestinal tract after oral administration. The microbiologically active 14(R)-hydroxyclarithromycin is formed by first pass metabolism. Clarithromycin, may be given without regard to meals as food does not affect the extent of bioavailability. Food does slightly delay the onset of absorption of clarithromycin and formation of the 14-hydroxy metabolite. Although the pharmacokinetics of clarithromycin are non linear, steady state is attained within 2 days of dosing. 14- Hydroxyclarithromycin is the major urinary metabolite and accounts for 10-15% of the dose.
Most of the remainder of the dose is eliminated in the faeces, primarily via the bile. 5-10% of the parent drug is recovered from the faeces.

Clarithromycin provides tissue concentrations that are several times higher than circulating drug level. Increased levels of clarithromycin have been found in both tonsillar and lung tissue. Clarithromycin penetrates into the middle ear fluid at concentrations greater than in the serum. Clarithromycin is 80% bound to plasma proteins at therapeutic levels.

Klacid Paediatric Suspension does not contain tartrazine or other azo dyes, lactose or gluten.